Trial record 1 of 1 for:    NCT00884676
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Ixabepilone and Sunitinib Malate in Treating Patients With Progressive Advanced Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Pfizer
Information provided by (Responsible Party):
Jaime Merchan, University of Miami
ClinicalTrials.gov Identifier:
NCT00884676
First received: April 18, 2009
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone when given together with sunitinib malate in treating patients with progressive advanced solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: Ixabepilone
Drug: Sunitinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Weekly and Every Three Weeks Ixabepilone and Sunitinib in Solid Tumor Patients

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Safety and toxicity profile as assessed by NCI CTCAE version 3.0 [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: Yes ]
  • Recommended Phase II dose of Ixabepilone when administered with Sunitinib [ Time Frame: Schedule A (12 - 18 months); Schedule B (6 -12 months after Schedule A) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic profiles of Ixabepilone and Sunitinib malate and correlation with activity and/or toxicity [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]
  • Efficacy data (complete response, partial response, or stable disease) of these treatment combinations [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]
  • Correlation of changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]
  • Estimation of optimal biological dose [ Time Frame: Approximately 18-30 months ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: November 2008
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Schedule A
Schedule A: Ixabepilone - Weekly for 3 weeks each cycle (Days 1, 8 and 15) For both Schedules A and B, Sunitinib daily, orally, starting on Day 8 of Cycle 1
Drug: Ixabepilone

Administered intravenously. Dosage assigned by Phase I center as determined by dose-escalation schedule:

  • Schedule A: Weekly for 3 weeks each cycle (Days 1, 8 and 15)
  • Schedule B: Day 1 of each 3-week cycle.
Other Names:
  • BMS-247550
  • Ixempra
  • Azaepothilone B
  • epothilone B lactam
  • Epothilone-B BMS 247550
Drug: Sunitinib
For both Schedules A and B, daily, orally, starting on Day 8 of Cycle 1
Other Names:
  • Sunitinib Malate
  • Sutent
  • Butanedioic acid
Experimental: Schedule B
Ixabepilone - Day 1 of each 3-week cycle For both Schedules A and B, Sunitinib daily, orally, starting on Day 8 of Cycle 1.
Drug: Ixabepilone

Administered intravenously. Dosage assigned by Phase I center as determined by dose-escalation schedule:

  • Schedule A: Weekly for 3 weeks each cycle (Days 1, 8 and 15)
  • Schedule B: Day 1 of each 3-week cycle.
Other Names:
  • BMS-247550
  • Ixempra
  • Azaepothilone B
  • epothilone B lactam
  • Epothilone-B BMS 247550
Drug: Sunitinib
For both Schedules A and B, daily, orally, starting on Day 8 of Cycle 1
Other Names:
  • Sunitinib Malate
  • Sutent
  • Butanedioic acid

Detailed Description:

OBJECTIVES:

Primary

  • To determine the safety and toxicity profile of ixabepilone in combination with sunitinib malate in patients with progressive, advanced non-hematologic malignancies.
  • To determine the recommended phase II dose of ixabepilone given weekly versus once every three weeks in combination with a fixed dose of sunitinib malate in these patients.

Secondary

  • To evaluate the pharmacokinetic profiles of the combination of ixabepilone and sunitinib malate and correlate them with activity and/or toxicity.
  • To obtain preliminary efficacy data (complete response, partial response, or stable disease) of these treatment combinations.
  • To correlate changes in angiogenesis biomarkers with clinical (safety and efficacy) and pharmacokinetic parameters in patients treated with these drug combinations.
  • To estimate the optimal biological dose.

OUTLINE: This is a dose escalation study of ixabepilone. Patients are assigned to 1 of 2 treatment groups.

  • Schedule A: Patients receive ixabepilone IV on days 1, 8, and 15. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Schedule B: Patients receive ixabepilone IV on day 1. Beginning on day 8 of course 1, patients also receive oral sunitinib malate once daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for biomarker and pharmacokinetic studies by flow cytometry.

After completion of study therapy, patients are followed at 30 days and every 3 months for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Non-hematological malignancy that has progressed on standard therapy.
  • Age > 18.
  • ECOG Performance Status (PS) 0, 1, or 2.
  • Life expectancy of > 3 months.
  • More than three prior systemic therapy regimens (a period of 4 weeks from chemotherapy or immunotherapy ("washout period"), must have elapsed; and 2 weeks for prior tyrosine kinase inhibitors).
  • Prior treatment with sunitinib in a 4 weeks on/2weeks off schedule is acceptable.
  • Women of Child Bearing Potential (WOCBP) must use adequate method of contraception throughout and up to 4 weeks after the study.
  • Patients must have either measurable disease (defined in Section 9.0) or evaluable disease (bony lesions, pleural effusion, ascites)
  • Required laboratory values obtained <= 7 days prior to registration:

    • Granulocytes (ANC) >= 1500/mm3
    • PLT >= 100,000/mm3
    • Hgb >= 9.0 g/dL
    • Direct bilirubin <= 1.0 x ULN
    • Alkaline phosphatase <= 2.5 x ULN (<= 5 x if liver metastasis is present)
    • AST/ALT <= 2.5 x ULN (<= 5 x if liver metastasis is present)
    • Creatinine < 1.5 x ULN
    • Pregnancy Test Negative (For WOCBP*)
    • Urinalysis - Urine protein/creatinine ratio < 1, or < 1+ protein**
    • TSH = WNL
    • INR <= 1.5, unless the patient is on full dose warfarin or stable dose of LMW heparin with a therapeutic INR of > 1.5, <= 3.

      • Urine protein should be screened by random urine protein:creatinine ratio. For urine protein: creatinine ratio >1.0, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment.
  • Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
  • Willingness to donate blood for correlative marker studies.
  • If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:
  • The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin.
  • No active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices).

EXCLUSION CRITERIA:

  • Patients with symptomatic/untreated CNS metastases. Patients with known CNS metastases can be enrolled if:
  • CNS metastases have been appropriately treated. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or resection as deemed appropriate by the treating physician. Patients who had surgical resection of CNS metastases or brain biopsy within 3 months prior to Day 1 will be excluded.
  • No ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
  • No evidence of progression or hemorrhage after treatment (brain imaging study within 4 weeks of treatment start).
  • CTC Grade 2 or greater neuropathy (motor or sensory) at study entry.
  • Inability to swallow capsules.
  • History of gastrointestinal disease, malabsorption, or requiring use of a feeding tube.
  • Patients who have received any investigational compound within the past 28 days (within 2 weeks for prior RTKI treated patients).
  • Patients who have received radiotherapy for any cause less than 4 weeks prior to study entry.
  • Patients taking cytochrome P450 (CYP) 3A4 enzyme-inducing or enzyme-inhibitor medications like: antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), St John's Wort, ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucolol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit (or juice) within two weeks of registration and during the course of therapy. Topical and inhaled steroids are permitted. Please refer to Appendix VI for a complete list of CYP34A inducers and inhibitors.
  • Patients with known HIV infection are excluded due to the possibility of unknown side effects on the immune system by these agents. The potential impact of pharmacokinetic interactions of anti-retroviral therapy with ixabepilone or sunitinib is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.
  • Invasive procedures defined as follows:

    • Major surgical procedure, open biopsy or significant traumatic injury <= 28 days prior to registration.
    • Anticipation of need for major surgical procedures during the course of the study.
    • Core biopsy <= 7 days prior to registration.
    • Port placement <= 7 days prior to registration.
    • Serious or non-healing wound, ulcer or bone fracture.
    • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess <= 28 days.
  • Evidence of bleeding diathesis or coagulopathy.
  • Ongoing hemoptysis, or cerebrovascular accident <= previous 6 months, or peripheral vascular disease with claudication on < 1 block, or history of clinically significant bleeding.
  • Significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, III or IV), angina pectoris requiring nitrate therapy, or recent myocardial infarction (<= the last 6 months). Patients must have an absolute baseline left ventricular ejection fraction (LVEF) >= 50% by MUGA scan within 4 weeks prior to registration
  • Uncontrolled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 90 mmHg diastolic on medication).
  • A currently active second malignancy other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy if they have completed anti-cancer therapy and are considered by their physician to be at less than 30% risk of relapse.
  • Any of the following, as this regimen may be harmful to a developing fetus or nursing child:

    • Pregnant women
    • Breastfeeding women
    • Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown.
  • Other uncontrolled serious medical or psychiatric condition (e.g. cardiac arrhythmias, diabetes, etc.)
  • Patients must not have ongoing ventricular cardiac dysrhythmias of NCI CTCAE Version 3.0 grade >= 2. Patients with a history of serious ventricular arrhythmia (VT or VF >= 3 beats in a row) are also excluded. Additionally, patients with ongoing atrial fibrillation are not eligible.
  • Patients must have a QTc interval < 500 msec on baseline EKG.
  • Prior treatment with ixabepilone.
  • History of chronic or recurrent infection that requires continuous use of anti-viral, anti-fungal or anti-bacterial therapy; or foreseeable need to receive anti-infective therapy within 14 days of Cycle 1 Day 1 treatment.
  • History of Grade 3/4 hypersensitivity reaction to Cremophor EL or its derivatives (polyoxyethylated castor oil).
  • Non-small cell lung cancer (NSCLC) of squamous cell type, or NSCLC of any histology that involves a major blood vessel (e.g. aorta, pulmonary artery, etc)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00884676

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Sponsors and Collaborators
Jaime Merchan
Bristol-Myers Squibb
Pfizer
Investigators
Principal Investigator: Jaime R. Merchan, MD University of Miami
  More Information

Additional Information:
No publications provided

Responsible Party: Jaime Merchan, Associate Professor, University of Miami
ClinicalTrials.gov Identifier: NCT00884676     History of Changes
Other Study ID Numbers: 20080376, SCCC-2008001, BMS-SCCC-2008001
Study First Received: April 18, 2009
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Epothilone B
Epothilones
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 22, 2014